In the last 50 years computers have made dramatic progress in their capabilities, but at the same time their failings have demonstrated that we, as designers, do not yet understand the nature of intelligence. Chess playing, for example, was long offered up as an example of the unassailability of the human mind to Artificial Intelligence, but now a chess engine on a smartphone can beat a grandmaster. Yet, at the same time, computers struggle to beat amateur players in simpler games, such as Stratego, where sheer processing power cannot substitute for a lack of deeper understanding. The task of developing that deeper understanding is overwhelming, and has previously been underestimated. There are many threads and all must be investigated. This dissertation explores one of those threads, namely asking the question "How might an artificial agent decide on a sensible course of action, without being told what to do?". To this end, this research builds upon empowerment, a universal utility which provides an entirely general method for allowing an agent to measure the preferability of one state over another. Empowerment requires no explicit goals, and instead favours states that maximise an agent's control over its environment. Several extensions to the empowerment framework are proposed, which drastically increase the array of scenarios to which it can be applied, and allow it to evaluate actions in addition to states. These extensions are motivated by concepts such as bounded rationality, sub-goals, and anticipated future utility. In addition, the novel concept of strategic affinity is proposed as a general method for measuring the strategic similarity between two (or more) potential sequences of actions. It does this in a general fashion, by examining how similar the distribution of future possible states would be in the case of enacting either sequence. This allows an agent to group action sequences, even in an unknown task space, into 'strategies'. Strategic affinity is combined with the empowerment extensions to form soft-horizon empowerment, which is capable of composing action policies in a variety of unknown scenarios. A Pac-Man-inspired prey game and the Gambler's Problem are used to demonstrate this selfmotivated action selection, and a Sokoban inspired box-pushing scenario is used to highlight the capability to pick strategically diverse actions. The culmination of this is that soft-horizon empowerment demonstrates a variety of 'intuitive' behaviours, which are not dissimilar to what we might expect a human to try. This line of thinking demonstrates compelling results, and it is suggested there are a couple of avenues for immediate further research. One of the most promising of these would be applying the self-motivated methodology and strategic affinity method to a wider range of scenarios, with a view to developing improved heuristic approximations that generate similar results. A goal of replicating similar results, whilst reducing the computational overhead, could help drive an improved understanding of how we may get closer to replicating a human-like approach.

by Ka Wai Wong. / "June 1999." / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / by Ka Wai Wong.

by Shao Bing. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (p. 111-122). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

In Nature, antibodies are capable of recognizing a huge variety of different molecular structures on the surface of antigens. The primary factor that defines the structural diversity of the antibody antigen combining site is the length variation of the complementarity determining region (CDR) loops. Following antigen stimulation, further diversification through the process called somatic hypermutation (SHM) leads to antibodies with improved affinity and specificity. Sequence diversification by SHM is mainly achieved by introduction of point substitutions and a small percentage of insertions/deletions (indels). Although the percentage of indels in affinity matured antibodies is low, probably due to the low rate incorporation of in-frame indels throughout the course of the SHM diversification process, it is likely that the antibody fold can accommodate higher diversity of affinity-enhancing indels. By in vitro evolution, other researchers have sampled either only restricted diversity of indels or extended diversity of insertions only in specific positions chosen based on structural information and natural length variation. The aim of this thesis was to study the impact of random and high diversity indels on antibody affinity by in vitro evolution. New approaches for construction of libraries with in-frame amino acid indels were applied to enable sampling of indels of different lengths across the entire antibody variable domains. I followed two different approaches for construction of indel libraries. Firstly, a recently developed random approach allowed the construction of libraries with random insertions and deletions. Secondly, a semi-random approach was developed to build libraries with different lengths of insertions that could be widely applied in future in vitro antibody affinity maturation campaigns. Libraries constructed by either of these approaches yielded variants with insertions with improved affinity. Overall, this thesis demonstrates that insertions besides offering alternative routes to affinity maturation can also be combined with point substitutions to take advantage of additive effects on function.

There is increasing evidence that hydrogen peroxide (H2O2) can act as a signalling molecule capable of modulating a variety of biochemical and genetic systems. Using Jurkat T-lymphocytes, this study initially investigated the involvement of H2O2 in the activation of a specific signalling protein extracellular signal-regulated protein kinase (ERK). It was found that as a result of H2O2 treatment, mitochondrial complex activities decreased which led to subsequent increase of mitochondrial reactive oxygen species (ROS) production. The increase of ROS resulted in higher cellular H2O2 as well as increased ERK activation. This study demonstrated that in an oxidative stress setting, H2O2 production from the mitochondria was an essential component in maintaining the activation of a signalling protein. One way in which H2O2 could influence protein function is by the oxidation of susceptible thiol groups of cysteine residues. To further understand the variety of signalling pathways that H2O2 may be involved in, an improved proteomics technique was developed to globally identify proteins with susceptible thiol groups. The

Pyrazolopyrimidines are a general class of compounds which exhibit Aj adenosine receptor affmity. A number of pyrazolo(3,4-d)pyrimidine analogues of isoguanosine and i-methylisoguanosine has been synthesised. All compounds were tested forAi adenosine receptor affinity using a (311) R-PIA competitive binding assay. The N-i and N-5 positions were substituted with a number of different ailcyl and aryi groups. 3-Chiorophenyl substitution of the N-i position and butyl substitution of the N-5 position greatly enhanced the overall adenosine receptor affinity. Substitution by a methyl group at the N-7 position fixed the C-4 position in the imino tautomeric form. This resulted in a marked reduction in activity. The substitution of the N-2 position with a phenyl group produced an analogue with a similar structure to i,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX). A 2-phenyl substituent was favourable for interaction with the adenosine receptor. A number of pyrazolo(3,4-d)pyrirnidine analogues of 4,6-bis-a-carbamoylethylthio-i-phenylthiopyrazolo(3,4-d)pyrinhidine (DJB-KK) has also been synthesised and tested for Aj adenosine receptor affinity. 4,6-Bis-alkylthio-1-phenylpyrazolo(3,4-d)pyrimidines with a-carbamoylethyl and u-carbamoylpropyi groups were compared. The additional methyiene of the a-carbamoylpropyl group produced increased adenosine receptor affinity. 6-a-Carbamoylethylthio-4-mercapto-1-phenylpyrazolo(3,4-d)pyrimidine and 4-cc-carbamoylethylthio- i-phenylpyrazolo(3,4-dlpyrimidine were compared. Substitution of the C-6 position maintained activity, while substitution of the C-4 reduced activity.

Sorption of non-ionic organic compounds to organic matter is usually characterized as a partitioning interaction, which is quantified by K [subscript]oc, the organic-C normalized partitioning coefficient. However K [subscript]oc for any single compound varies considerably between soils, often by a factor of 3-10. This study addresses some of the potential causes of this variability. Forty-four soil cores were collected from a 2 ha paddock. Ten of these cores were selected for sorption measurements. The chemical composition of the soil organic matter (SOM) was determined using ¹³C NMR analysis. It was found that K [subscript]oc for diuron was positively correlated with aryl C (r² = 0.59) and negatively correlated with O-alkyl C (r² = 0.84). There were no such correlations for phenanthrene K [subscript]oc. A second set of experiments was carried out to investigate the effects of SOM– mineral interactions on the sorption properties of a selection of the soils. It was found that HF-treatment increased K [subscript]oc for both phenanthrene and diuron. The HF treatment removes mineral matter leaving the organic phase unaffected by the treatment. The increase in K [subscript]oc on HF-treatment soils provides strong evidence that interactions between organic matter and soil minerals block organic matter sorption sites. Furthermore, following HF-treatment, there was a positive correlation between K [subscript]oc for phenanthrene and aryl C and carbonyl C and a negative correlation with O-alkyl C. This suggests that the non-constancy of the relationship between organic matter chemistry and K [subscript]oc, for whole soils in the case of phenanthrene, may be a consequence of variability of the effect of organic matter-mineral interactions on K [subscript]oc. The influence of lipids on the sorption of diuron and phenanthrene to soils was also investigated. Lipids are known to cover the surfaces of organic matter in soil. K [subscript]oc for diuron and phenanthrene were consistently higher for the lipid-extracted soils than for the whole soils (average of 31% for diuron and 29% for phenanthrene), indicating that lipids block sorption sites on the organic matter. Sorption experiments on one pair of HF-treated soils indicated that the blocking effects of minerals and lipids are independent, because lipid extraction and HF-treatment combined increased K [subscript]oc by more than either treatment alone. In the last experiment, the effect of solvent conditioning on the sorption of diuron and phenanthrene was investigated. The K [subscript]oc values for compounds were consistently higher for solvent-treated whole soil and lipid-extracted soil than corresponding soils before solvent treatment. Solid-state ¹³C NMR spectra of the solvent-treated soils indicated that there were no significant changes in the chemical structure of SOM caused by solvent treatment. Solvent treatment changes the physical conformation of the SOM, increasing its sorption affinity. The key findings from the research are: • Variations in sorption affinity for diuron are related to differences in the soil organic matter chemistry. • SOM-mineral interactions can have a substantial influence on K [subscript]oc for non- ionic compounds. • Lipids may block the active sorption sites on the SOM thereby diminishing sorption overall. • Solvent conditioning can change the physical conformation of SOM and lead to enhancement sorption of diuron and phenanthrene. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1372068 / Thesis (Ph.D.) - University of Adelaide, School of Earth and Environmental Sciences, 2009

Thesis (Ph.D.)--Baylor University, 2005. / Includes bibliographical references (p. 259-273).

Cardiac diseases associated with mutations in Tn subunits include hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and restrictive cardiomyopathy (RCM). Altered calcium handling in these diseases is evidenced by changes in the Ca2+ sensitivity of contraction. Mutations were generated to increase/ decrease the Ca2+ sensitivity of skinned fibers, and create the classified effects of DCM, HCM and RCM. This study mimicked the changes in Ca2+ sensitivity and relaxation properties of the muscle to determine if this was sufficient to recreate the disease. Four mutants (A23Q, S37G, V44Q, L48Q) were identified with RCM-like properties; a large increase in Ca2+ sensitivity, increased basal force and loss of ATPase inhibition. Two mutations were identified (E40A, I61Q) with DCM properties; decreased Ca2+ sensitivity in skinned fibers, decreased force recovery (%), and decreased activation of the ATPase at high Ca2+ levels (pCa 6-4). Also, the functional effects of four newly identified cTnC mutations associated with HCM were reported. Three of these HCM mutations A8V, C84Y, and D145E displayed HCM characteristics, increased Ca2+ sensitivity in skinned fibers and ATPase and A8V and D145E increased the force recovery. Only, D145E significantly increased the ATPase activation of the reconstituted thin filament. Also, Ca2+ affinity measurements using IAANS fluorescence were performed. No significant changes were found for E134D. The C84Y IAANS fluorescence measurements revealed that cTnC Ca2+ affinity of the cTn complex was unaltered. The Ca2+ affinity increased for D145E in isolated cTnC and the cTn complex, however in the regulated thin filament (RTF) with myosin subfragment-1 (S1) and rigor crossbridges the Ca2+ affinity values were similar to the fiber Ca2+ sensitivity. For A8V, the RTF significantly increased the Ca2+ affinity, and addition of S1 and rigor crossbridges caused the values to parallel the Ca2+ sensitivity values. In conclusion, direct and indirect protein-protein interactions contribute to the enhanced Ca2+ sensitivity of the HCM mutants. The cTnC mutant screen allowed selection of mutations that mimic the disease states: S37G (RCM) and, E40A (DCM); A8V (HCM) from the patient study for analysis in knock-in mice for futures studies to determine if these disease states can be recapitulated in vivo.

Purpose: To identify the relevance ethnocentrism, affinity and product country-image (the three theory effect affectionately called “the enchilada effect” by the authors) have on the consumers’ decision-making process as well as their effect on the consumers’ preferences for certain product attribute importance and types. Problem: In modern society most marketplaces around the world are full of foreign products. The importance ethnocentrism and the country of origin (COO) effect have on the consumers’ decision process has already been studied and identified on several researches along several decades. This mentioned, the authors think not only ethnocentrism, but also affinity and PCI might have an effect on this decision process as well. Therefore, they believe this to be an interesting and important consumer behavior phenomenon to investigate. Further, they want to identify how much these theories influence the consumers in two areas: first, the relative preferences of 8 attributes importance (price, quality, design, weight, energy saving, capacity, material, and HDD storage capacity) distributed in 4 product categories (laptops, refrigerators, bicycles and shoes); and second, their effect on consumers’ preferences over two types of product versions (low-end versus high-end) that differ in price and their added features with the basic price-quality relationship i.e. the more expensive the better it is.